A Nobel prize for medicine for the understanding of body clocks

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NOBEL week, a round of lectures and ceremonies held every December in Stockholm, which climaxes with the award of the prizes themselves and a subsequent banquet, is a leisurely affair. Since prize-winners come from all over the world, that is a good thing. It gives them time to recover from their jet-lag before they meet the King of Sweden, and the medals and cheques are handed over. This year, three of the prize-winners may be particularly appreciative of that, for they are some of the scientists who have helped to explain why jet lag exists in the first place.

Jeffrey Hall, Michael Rosbash and Michael Young are, between them, responsible for working out how the endogenous clocks of fruit flies—and, by extension, of other organisms—run what is known as the circadian rhythm. This is the internal cycle (circa is the Latin for “about” and dies the Latin for “day”) that matches the body’s physiology to the alternation of light and darkness caused by Earth’s rotation. In human beings it controls, among many other things, sleep patterns. Hence the discovery, once the invention of the jet engine made rapid travel across time zones possible, that someone flying from, say, London to New York, will take several days to adjust to solar time as New Yorkers perceive it.

Dr Hall and Dr Rosbash worked together at Brandeis University, in Massachusetts. Dr Young operated separately, at Rockefeller University, in New York. Between them, studying mutated fruit flies, they put together an explanation of what is going on at a molecular level.

Their first step, in 1984, was the isolation within the fruit-fly genome of a gene called period, which had previously been found to be important in controlling circadian rhythms. At a time when gene sequencing was in its infancy, this was remarkable enough. Dr Hall and Dr Rosbach then went on to measure the concentration in fly brains of the protein this gene encodes. They discovered that the protein’s concentration cycles predictably over the course of 24 hours, peaking at night. They also measured levels of the messenger molecule, produced by period genes, which carries the recipe for the protein to a cell’s protein-making machinery. That, too, cycles daily—peaking a few hours before concentration of the protein itself is at its highest.

The crucial part of the story is that the protein inhibits the action of period genes. The more of the protein there is, the less active the genes are. That reduces production of the messenger molecule, which reduces production of the protein, which permits the gene to reactivate. And so on.

Lots of other genes and proteins are involved as well—many of which were also discovered by Dr Hall, Dr Rosbash and Dr Young. Some of these serve to link the clock to information from the eyes, permitting it to stay in synchrony with the sun. But it is the underlying cycle of period gene activity, regulated by the messenger molecule and the protein, that is the actual pendulum of the biological clock.